Vaginitis is a non-specific term describing symptoms such as irritation and/or inflammation of the vagina that affects millions of women each year. Vaginal infections produce a variety of symptoms, such as discharge, itching, burning, pain, swelling, odor, painful urination or bleeding. Infectious forms of vaginitis can be caused by bacteria, viruses, protozoa, parasites, or an overgrowth of ‘filamentous’ (hyphal and pseudohyphal) yeast, primarily the Candida species. The two most common types vaginal infections are VulvoVaginal Candidiasis (VVC), also known as yeast vaginitis, and Bacterial Vaginosis (BV). Yeast (primarily Candida albicans) are dimorphic fungi and are normal inhabitants of skin and body cavities. Candida species can become a problem or pathogenic when they become virulent under the influence of heat, a required condition for the pathogenesis of VVC. Other risk factors for the development of VVC besides heat and moisture are sunbathing, swimming, exercise, sexual intercourse, oral sex, tight fitting pants, panty hose, non-cotton crotched underwear, and thongs. Antibiotics, oral steroids, pregnancy, immunosuppressed states, diabetes mellitus, urinary incontinence, and some medications (oral contraceptives) can predispose a woman to recurrent VVC. Beside nutrient restriction, pH changes, CO2, and serum, the requirement for an elevated temperature is essential for the yeast to change size and shape by morphing into their ‘filamentous’ forms (hyphal and pseudohyphal). These ‘filamentous’ forms are responsible for the invasive disease state known as VVC. Candida albicans (C. albicans) and other species may form biofilms as a result of VVC which results in the persistence of the condition and resistance to treatment. The mechanism by which C. albicans are able to change their morphology is due to the increased production of HSP 90 (heat shock proteins by C. albicans and other species with similar proteins) which occurs as a direct result of elevated temperatures. This ‘heat’ requirement for yeast to change into their virulent, filamentous forms has remained enigmatic.
Bacterial vaginosis (BV) is the most prevalent cause of infectious vaginitis accounting for about 40-45% of all cases. It is distinguished by a malodorous vaginal discharge that is adherent to the vaginal mucosa of body cavities. While Gardnerella vaginalis is associated with the condition, BV is thought to be a synergistic, polymicrobial infection of pathogens, primarily anaerobic, such as Atopium vaginae, mobiluncus, bacteroides, ureoplasma, mycoplasma, fusobacterium, among many others. As these pathogens and normal flora multiply, forming a biofilm, they elaborate chemicals and waste products known to elevate the pH and produce the characteristic ‘amine’ malodorous discharge. It is this biofilm that allows the bacteria of BV to remain resistant to antibiotic treatment and to frequent recurrences. Biofilms (‘Surface Slimes’) are adherent communities of microorganisms, held together by a polymeric matrix of polysaccharides, proteins, and nucleic acids. Biofilms and their biologic components such as bacteria, yeast, virus, and their metabolic waste products are electrostatically negatively charged. Current studies are underway to find enzymatic or electromagnetic dissolution, so that lactic acid and hydrogen peroxide (H2O2) can be restored via their production by the normal bacterial flora, known as lactobacillus. Lactobacillus crispatus predominates in an healthy vagina. The current device will introduce temperature reduction to the tissue and adherent biofilm, to disrupt the biofilm with the optional addition of a coating compound such as pH normalizing or acidifying agent to help normalize the vaginal pH. The elevation in pH from BV probably occurs at a much later stage and is one of the reasons that vaginal applications hydrogen peroxide (H2O2) and lactic acid have less effect on the persistence of the biofilm, and account for recurrences of BV. Results from research studies show that biofilms exist ‘in vitro’ at temperatures of 37° C., making biofilms also temperature sensitive, especially at lowered tissue temperatures. Biofilms start to break down at less than 30 C and higher oxygen levels. Therefore, the optional addition of hydrogen peroxide to a cooling device inserted into a body cavity will release oxygen and hydrogen ions that will increase the oxygen content of the vagina which causes the self-destruction of biofilms, will help restore the pH balance (acidification via H+ ion release), and encourage the re-colonization of lactobacilli species in the vaginal epithelium, since this species does not live in biofilms, nor is it temperature sensitive. Lactobacilli produce hydrogen peroxide and lactic acid to keep the vaginal at a normal pH of about 3.5-4.5. Thus, the tissue cooling effect of this intra-vaginal device described in the invention, will simultaneously disrupt biofilms, allow easier penetration of any necessary chemicals or agents, and allow the normal flora of lactobacillus species to grow normally and restore the vagina to its normal pH.
The bacteria of BV are both anaerobic and facultative anaerobic and grow best under conditions with little or no oxygen. Fortunately, lactobacilli are facultative anaerobes and tolerate both conditions, but flourish best in the presence of oxygen.
Biofilms on the skin and in body cavities resist removal by conventional soap and water. A mechanism that could prove essential in helping with the treatment and cure of these conditions is that the pathogens' biofilms may be disrupted simply by the mechanical separation of the vaginal (body cavity) walls, the lowering of the temperature of the vaginal tissue, or by applying an agent with an electrostatic positive charge to cause adherence of the negatively charged exopolysaccharide biofilms. For instance, polylysine, a cationic (positively charged) polypeptide used as a food preservative, can adhere to a cell's surface, causing clumping and cessation of protein synthesis, thus preventing spoilage via biofilm formation. BV is dependent on the biofilm for disease persistence and low cure rates of approximately 80%, and biofilms in VVC are less well understood as far as pathogenesis and persistence, but may be a factor in more advanced cases or in persons with underlying conditions such as diabetes, pregnancy, or immune-suppressed states.
Other causes of vaginitis may include vulvodynia and vestibulitis, conditions suspected to be caused by repetitive treatment with antifungal creams and repetitive antigenic exposure to Candida yeast species. This infectious destruction of tissue may result in poor healing due to repetitive and over active immune responses, possibly causing permanent ‘neuralgias’ or autoimmune ‘self’ destruction of tissue with resultant scarring, recalcitrant pain and burning. Since these conditions (vestibulitis and vulvodynia) are incurable and have poor response to therapies, the present invention has the potential to prevent the need for repetitive chemical anti-fungal drug exposures, thus preventing the occurrence of these conditions in the first place.
There are over eighty-one varieties of yeast, three of which are Candida albicans, Candida tropicalis, Candida glabrata, while C. parapsilosis, C. kefyr, C. krusei are considered less common causes of VVC. For the most common species, Candida albicans accounts for 85-90% of cases of VVC, and the over-the-counter remedies now available will treat and cure this type of yeast only 80% of the time. Current treatment for C. tropicalis, C. glabrata, and the others are by physician prescribed antifungal creams only. All current over-the-counter antifungal creams treat only one form of VVC (Candida albicans), and take days, not hours to be effective.
The current treatment systems use medicine/drugs (either oral or topical) to treat VVC and BV. Likewise, there are no over-the-counter treatments for other types of pathogens in the vagina like trichomonas, gonorrhea, chlamydia, herpes, gardnerella (known to be a factor in BV) or any other, yet to be identified pathogen. The current therapies require the use of anti-fungal or anti-microbial creams/semisolids or oral tablets. When the drug melts in the vagina, it spills out onto the perineum and causes more itching, burning, and pain, exacerbating the symptoms associated with VVC and BV. These emulsions contain many synthetic chemicals and preservatives, which are known to be caustic and allergenic to human skin and mucous membranes. These chemicals, most notably methyl parabens, propylene glycols, cetyl alcohols, sodium lauryl sulfates are caustic to the skin, yet are used routinely in the current antifungal medicines and other therapies (which do nothing more than treat the itch symptom). Most clinicians believe there is an underreporting of these skin reactions, thought to be a result of the over-the-counter manner in which the condition is treated, and due to the fact that the toxic skin reactions mimic the symptoms of VVC, for which a woman seeks relief in the first place. Another problem with OTC and prescription anti-fungal medications is that their mechanism of action (destruction of the yeast cell membrane/wall) results in the release of the cell's toxic contents (enzymes). These released enzymes result in tissue destruction via the mechanism by which Candida are able to penetrate tissue and invade the host. This increases the intensity of the symptoms by inflaming the already diseased tissue, prolonging the symptoms for days, before any symptomatic relief is experienced.
Because the woman is confused by the claims of over-the-counter (OTC) medications due to the worsening of her symptoms, she is frustrated as her condition worsens until she either buys more irritating creams or visits her doctor. With regard to BV, there are no OTC remedies for this condition, yet douche manufacturers routinely advocate douching as an effective remedy for vaginal odor, inferring that their products treat this condition. However, BV is known to be more common in women who douche, suggesting that douching chemicals are the actual cause or increase the risk of developing BV, rather than the solution. All obstetricians/gynecologists advise against douching for many well documented scientific reasons (primarily due to increasing the risk of BV, which is a known risk factor for both premature rupture of membranes and preterm births, as well as sexually transmitted diseases), yet the products persist, and are responsible for the recurring nature of the condition. Furthermore, the only treatment options for BV are either systemic (oral) or topical drugs such as Metronidazole and Clindamycin, among others, in the same category of medications. The toxicities for these two medications are noteworthy, with many side effects and drug-drug interactions, as well as possible teratogenicity in pregnancy. These medications are available by prescription only. The invention described herein provides a safe, non-chemical solution for both VVC and BV to help reduce the risk of acquiring vestibulitis/vulvodynia or delivering a premature infant. The cooling device is safer, works faster, and more effectively than chemical alternatives. A non-chemical option that has immediate symptomatic relief and a more effective remedy against all temperature sensitive pathogens and species of Candida, and the potential to have an impact on BV via reduction in biofilms and bacterial counts, is the basis for this invention.
Existing medicinal creams add moisture and substances that promote biofilm formation in the vagina, which is counterproductive to curing both VVC and BV. Yeast can survive many environmental conditions, but under normal pH and carbon dioxide levels, additional heat is necessary for yeast to change in size and shape (morphology), grow and multiply to invade tissue, resulting in tissue destruction, enzyme release, and escape from immune cells causing the condition known as VVC. Under normal body temperatures though, the mass destruction of lactobacilli via antibiotics, can result in a flare of VVC as a result of altered (increased pH). Candida albicans, which accounts for about 80-95% of VVC outbreaks, can only be grown in a laboratory setting on appropriate growth media at a minimum temperature of 36° C., which is 96.8° F.
Although current drugs do cure VVC infections about 80% of the time, they are not without significant side effects. Oral antifungal medicine also poses significant risks, such as drug interactions resulting in anaphylactic shock or even death. Oral antifungals (fluconazole) used to treat VVC can be compared to using a “bazooka to shoot a mouse”; and, fluconazole only treats one species of yeast, Candida albicans. 
Additional problems exist with currently available treatments for vaginitis caused by VVC. Current medications, while partially effective, may take 3-7 days to provide relief from itching, burning, swelling, and pain. In addition, both oral and topical drugs may adversely interact with other medications, such as antihistamines, antidepressants, asthma medications and the like. Life threatening anaphylaxis can result from oral systemic medications. Some topical medications can cause toxic skin reactions. Furthermore, the success rate of existing treatment methods range from 60-80% because a chosen drug may not be effective against all of the strains of Candida and due to anti-fungal drug resistance, an increasingly common problem due to the over-use or inappropriate use of both topical and oral anti-fungal medications. A need exists for a topical, non-chemical, method of treating both the symptoms and causes of VVC and BV infections within body cavities that is immediate, non-invasive, and effective against all yeast species, the bacterial overgrowth, and biofilms associated with BV, VVC, and other conditions.
Pregnancy is another predisposing condition whereby VVC and BV can cause significant health risks to the mother and the baby such as in preterm, premature rupture of membranes. No currently available medications have been studied in pregnancy for these two conditions, and as such, are placed in Category ‘C’, meaning unknown risk. A need exists for inhibiting pathologic fungal, microbial, viral, protozoan, and parasitic growth in a body cavity for both pregnant and non-pregnant women.